Influence of prenatal exposure to diethylstilbestrol on estrogen and progestin binding proteins in uteri and dimethylbenzanthracene- induced mammary tumors of the rat.
Various characteristics of steroid binding proteins from mammary tumors and uteri of rats exposed prenatally to diethylstilbestrol (DES) were examined. Pregnant rats were treated with no hormone (group A) or with a total dose of 1.2 micrograms DES during the second (group B) or third (group C) trimester of gestation. Female offspring received 7,12-dimethylbenz[a]anthracene (DMBA) at d 50 +/- 1. Animals with large mammary tumors were subjected to bilateral ovariectomy. Seven months after carcinogen treatment, the experiment was terminated. High-affinity binding sites for [3H] estradiol-17 beta and [3H]R5020 were found in all mammary tumors assayed. On sucrose gradients of low ionic strength both 8S and 4S forms of the estrogen receptor were identified in mammary tumors, regardless of prenatal treatment. In addition, progestin receptors sedimenting at 4S were identified in these tumors. However, the 7-8S form of the progestin receptor was found only in tumors from intact animals. Levels of progestin receptors were diminished after ovariectomy, both in mammary tumors and in uteri; ovariectomy also resulted in a significant reduction in uterine wet weight in the hormone exposure groups, as expected. Unlike groups A and B, rats exposed to DES during the third trimester had uterine progestin binding capacities and uterine wet weights that did not decrease proportionally ater ovariectomy. Furthermore, progestin binding capacities in mammary tumors from group C ovariectomized rats were higher than those in the other two groups. In intact rats from group C, cytosol from mammary tumors also had elevated levels of progestin binding; however, no differences in progestin binding were observed in the uteri from these animals. Small differences in estrogen binding capacities in tumor tissues were observed among the three groups; uterine estrogen binding capacities did not vary significantly. Prenatal exposure to DES during the third trimester appeared related to persistent biochemical alterations in rat mammary tumors and uteri; earlier exposure did not have this effect.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001551:Benz(a)Anthracenes; D002369:Castration; D004054:Diethylstilbestrol / Q000633:toxicity*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000139:chemically induced*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011397:Promegestone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000032:analysis* / Q000378:metabolism; D014599:Uterus / Q000032:analysis*
D001551:Benz(a)Anthracenes; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D004054:Diethylstilbestrol; D011397:Promegestone